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Postdoctoral Fellow

Ambar Kachale

Postdoctoral Fellow

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“If the first nucleotide in the anticodon is a C or an A, pairing is specific and acknowledges original Watson-Crick pairing, that is: only one specific codon can be paired to that tRNA”.

Codon-Anticodon pairing, The Wobble hypothesis,
F. H. C. Crick, J. Mol. Biol. (1966)

According to standard genetic code 61 sense codons dictate what amino acids will be incorporate into nascent proteins, 3 nonsense codons signal the end of decoding. A handful of eukaryotes evolved under conditions that led to partial reassignment of nonsense codons into sense codons. Remarkably, in the past few year’s two ciliates, a dinoflagellate and a trypanosomiasis (the latter only in silico) have been shown to have all three nonsense codons reassigned to sense codons, thus completely breaking the natural law of the genetic code. However, the molecular basis of this remarkable evolutionary departure from the canonical genetic code have remained elusive.

In the PhD thesis entitled “Short tRNACNN anticodon stem allows C: A wobble and stop codon reassignment” I described newly isolated trypanosomatid, which we named Blastocrithidia nonstop, with all three stop codons reassigned. By sequencing its genome, transcriptome and proteome, and by transferring some key experiments into genetically tractable Trypanosoma brucei and yeast, we were able to uncover molecular basis of its remarkable and extensive alteration of the genetic code that is, as we also document, utilized by other similarly challenged organisms as well.

During my postdoctoral research at Harvard University, my primary focus will be on gaining a structural understanding of HIV Tat and its competition with HEXIM:7SK. I will primarily utilize NMR techniques to explore various aspects of RNA structural biology.